Effects of Lithium Therapy on Ventricular Repolarization in Bipolar Disorder Patients

Yıl 2018, Cilt: 21 Sayı: 3, 193 - 197, 02.12.2018

Cemil Zencir , Kadir Karakuş Oktay Kocabaş Gökhan Bahtiyar Mithat Selvi Kayıhan Karaman

Öz

Introduction:
Bipolar disorder (BD) is a
significant mental health concern in the world. Most of the drugs used in the
treatment of bipolar disease may cause life-threatening arrhythmias by
affecting the distribution of ventricular repolarization (VR). VR is commonly
assessed using QT interval and Twave measurements. The aim of this study was to
evaluate VR using the T peak to T end (Tp-e) interval and the Tp-e/QT ratio and
to investigate the relationship between lithium therapy and VR parameters in
patients with BD.

Patients
and Methods: Forty-six BD
patients under lithium therapy and 45 participants in a control group were
included in our study. The Tp-e interval and Tp-e/QT ratio were measured using
12derivation electrocardiography (ECG). These parameters were compared between
groups.

Results:
The QT
interval (p= 0.01), QTc interval (p= 0.003), Tp-e interval (p< 0.001), and
Tpe/QT ratio (p= 0.009) were significantly higher in patients with BD than in
the control group. There was a positive correlation between the Tp-e interval
and serum lithium levels (r= 0.317, p< 0.032). In addition, the increased
serum lithium level (β= 0.398, p= 0.007) was found to be an independent
predictor of the prolonged Tp-e interval.

Conclusion:
Prolonged
Tp-e interval may be a useful indicator of increased risk of ventricular
arrhythmia in patients using lithium therapy.

Anahtar Kelimeler

Bipolar disorder, lithium, Tp-e interval, ventricular repolarization

Bipolar Bozukluk Hastalarında Lityum Tedavisinin Ventriküler Repolarizasyon Üzerine Etkileri

Öz

Giriş: Bipolar bozukluk (BD) dünyada önemli bir
mental sağlık sorununudur. Bipolar bozukluk tedavisinde kullanılan ilaçların
çoğu, ventriküler repolarizasyonun (VR) dağılımını etkileyerek hayatı tehdit
eden aritmilere neden olabilir. VR genellikle QT aralığı ve T dalgası ölçümleri
kullanılarak değerlendirilir. Bu çalışmanın amacı, Tp-e intervali ve Tp-e/QT
oranını kullanarak VR’yi değerlendirmek ve bipolar bozukluğu olan hastalarda
lityum tedavisi ve VR parametreleri arasındaki ilişkiyi araştırmaktır.

Hastalar ve
Yöntem: Çalışmamıza lityum tedavisi alan 46 hasta ve 45 katılımcıdan
oluşan kontrol grubu dahil edildi. Tp-e aralığı ve Tp-e/QT oranı 12-derivasyon
elektrokardiyografi (EKG) kullanılarak ölçüldü. Bu parametreler gruplar arasında
karşılaştırıldı.

Bulgular: Bipolar bozukluk olan hastalarda QT interval (p= 0.01),
QTc interval (p = 0.003), Tp-e interval (p< 0.001) ve Tp-e / QT oranı (p=
0.009) kontrol grubuna göre anlamlı olarak yüksek bulundu. Tp-e intervali ile
serum lityum düzeyleri arasında pozitif korelasyon vardı (r= 0.317, p<
0.032). Ayrıca artmış serum lityum seviyesi (β= 0.398, p= 0.007), uzun Tp-e
aralığının bağımsız bir belirleyicisi olarak bulundu.

Sonuç: Uzamış Tp-e intervali, lityum tedavisi kullanan hastalarda artmış
ventriküler aritmi riskinin yararlı bir göstergesi olabilir.

Anahtar Kelimeler

Bipolar bozukluk, lityum, Tp-e interval, ventriküler repolarizasyon

Kaynakça

• 1. Demers RG, Heninger GR. Electrocardiographic T-wave changes during lithium carbonate treatment. JAMA 1971;218:381-6.
• 2. Tilkian AG, Schroeder JS, Kao JJ, Hultgren HN. The cardiovascular effects of lithium in man. Am J Med 1976;61:665-70.
• 3. Mitchell JE, Mackenzie TB. Cardiac effects of lithium in man: A review. J Clin Psychiatry 1982;43:47-51.
• 4. Montalescot G, Levy Y, Hatt PY. Serious sinus dysfunction caused by therapeutic doses of lithium. Int J Cardiol 1984;5:94-6.
• 5. Higham PD, Campbell RW. QT dispersion. Br Heart J 1994;71:508-10.
• 6. Kors JA, Ritsema van Eck HJ, Van Herpen G. The meaning of the Tp-Te interval and its diagnostic value. J Electrocardiol 2008;41:575-80.
• 7. Halboos A, Jockenhövel F. Complete atrioventricular block during lithium therapy within therapeutic range. Dtsch Med Wochenschr 2012;137:2583-5.
• 8. Paclt I, Slavícek J, Dohnalová A, Kitzlerová E, Pisvejcová K. Electrocardiographic dose-dependent changes in prophylactic doses of dosulepine, lithium and citalopram. Physiol Res 2003;52:311-7.
• 9. Gupta P, Patel C, Patel H, Narayanaswamy S, Malhotra B, Green JT, et al. T(p-e)/QT ratio as an index of arrhythmogenesis. J Electrocardiol 2008;41:567-74.
• 10. Day CP, McComb JM, Campbell RW. QT dispersion: an indication of arrhythmia risk in patients with long QT intervals. Br Heart J 1990;63:342-4.
• 11. Heviaet J C, Antzelevitch C, Bárzaga FT, Dorantes Sánchez M, Dorticós Balea F, Zayas Molina R, et al. Tpeak-Tend and Tpeak-Tend dispersion as risk factors for ventricular tachycardia/ventricular fibrillation in patients with the Brugada syndrome. J Am CollCardiol 2006;47:1828-34.
• 12. Haddad PM, Anderson IM. Antipsychotic-related QTc prolongation, torsade de pointes and sudden death. Drugs 2002;62:1649-71.
• 13. Wright D, Salehian O. Brugada-type electrocardiographic changes induced by long-term lithium use. Circulation 2010;122:418-9.
• 14. Sheehan DV, Lecrubier Y, Sheehan KH, Amorim P, Janavs J, Weiller E, et al. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatry 1998;59(Suppl 20):22-33.
• 15. Bazett HC. The time relations of the blood-pressure changes after excision of the adrenal glands, with some observations on blood volume changes. J Physiol 1920;53:320-39.
• 16. Cade JF. Lithium salts in the treatment of psychotic excitement. 1949. Bull World Health Organ 2000;78:518-20.
• 17. Dunner DL. Optimizing lithium treatment. J Clin Psychiatry 2000;61:76-81.
• 18. Wellens HJ, Cats VM, Duren DR. Symptomatic sinus node abnormalities following lithium carbonate therapy. Am J Med 1975;59:285-7.
• 19. Letsas KP, Weber R, Astheimer K, Kalusche D, Arentz T. Tpeak-Tend interval and Tpeak-Tend/QT ratio as markers of ventricular tachycardia inducibility in subjects with Brugada ECG phenotype. Europace 2010;12:271-4.
• 20. Singer I, Rotenberg D. Mechanisms of lithium action. N Engl J Med 1973;289:254-60.
• 21. Tilkian AG, Schroeder JS, Kao J, Hultgren H. Effects of lithium on cardiovascular performance: Report on extended ambulatory monitoring and exercise testing before and during lithium therapy. Am J Cardiol 1976;38:701-8.
• 22. Roberts-Thomson KC, Teo KS, Young GD. Drug-induced Brugada syndrome with ST-T wave alternans and long QT. Intern Med J 2007;37:199-200.
• 23. Altinbas K, Guloksuz S, Caglar I, Caglar FN, Kurt E, Oral ET. Electrocardiography changes in bipolar patients during long-term lithium monotherapy. Gen Hosp Psychiatry 2014;36(6):694-7.
• 24. Kurt E, Emul M, Ozbulut O, Guler O, Erdur F, Sağlam H, et al. Is valproate promising in cardiac fatal arrhythmias? Comparison of P-and Q-wave dispersion in bipolar affective patients on valproate or lithium-valproate maintenance therapy with healthy controls. J Psychopharmacol 2008;23:328-33.
• 25. Bucht G, Smigan L, Wahlin A, Eriksson P. ECG changes during lithium therapy. Acta Med Scand 1984;216:101-4.
• 26. Sagie A, Larson MG, Goldberg RJ, Bengtson JR, Levy D. An improved method for adjusting the QT interval for heart rate (the Framingham Heart Study). Am J Cardiol1992;70:797-801.
• 27. Chen PH, Tsai SY, Chung KH. Effects of medication and pathophysiology on 12-lead electrocardiograms in bipolar disorder and schizophrenia. Journal of Experimental & Clinical Medicine 2010;24:181-5.
• 28. Hsu CH, Liu PY, Chen JH, Yeh TL, Tsai HY, Lin LJ. Electrocardiographic abnormalities as predictors for over-range lithium levels. Cardiology 2005;103:101-6.